Characterization of cationic amino acid transporter and its gene expression in rat hepatic stellate cells in relation to nitric oxide production.
J Hepatol
; 29(6): 923-32, 1998 Dec.
Article
em En
| MEDLINE
| ID: mdl-9875639
ABSTRACT
BACKGROUND/AIMS:
Nitric oxide is a potent mediator of hepatic sinusoidal hemodynamics and affects hepatic stellate cells (Ito cells, fat-storing cells). Although nitric oxide production may depend on the induction of inducible nitric oxide synthase and on transport of extracellular L-arginine, the precise mechanisms controlling nitric oxide production in stellate cells have not been well characterized.METHODS:
Using stellate cells prepared from the male Wistar rat, kinetic analysis of L-arginine transport and reverse transcription-polymerase chain reaction for cationic amino acid transporter were carried out. The effect of tumor necrosis factor-alpha and interferon-gamma on L-arginine transport, mRNA expression of cationic amino acid transporter and inducible nitric oxide synthase, and nitric oxide production of stellate cells was assessed.RESULTS:
The L-arginine transport system functioning in the transformed hepatic stellate cells was system y+, possibly mediated by cationic amino acid transporter-1 and cationic amino acid transporter-2B (Km approximately 50 microM). Tumor necrosis factor-alpha enhanced cationic amino acid transporter-2B mRNA expression and L-arginine transport, whereas cationic amino acid transporter-1 mRNA expression remained unchanged. Interferon-gamma induced the expression of inducible nitric oxide synthase mRNA without obvious changes in L-arginine transport. Interferon-gamma in combination with tumor necrosis factor-alpha induced nitric oxide production with an enhancement in cationic amino acid transporter-2B mRNA expression, inducible nitric oxide synthase mRNA expression, and L-arginine transport, while extracellular L-lysine competitively inhibited this nitric oxide production.CONCLUSIONS:
In transformed hepatic stellate cells, tumor necrosis factor-alpha and interferon-gamma have a crucial role in nitric oxide production, and extracellular L-arginine transport and inducible nitric oxide synthase expression are regulated in a differential cytokine-specific manner. As the estimated Km of L-arginine transporter in transformed hepatic stellate cells is very similar to the physiological L-arginine concentration in portal vein, we assume that increased portal L-arginine concentration may easily affect sinusoidal blood flow through enhancement of autocrine nitric oxide production in transformed hepatic stellate cells of diseased liver.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Regulação da Expressão Gênica
/
Fígado
/
Proteínas de Membrana
/
Óxido Nítrico
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article